hcvm
DESCRIPTION
HCVM. Member of b -herpesvirus family >200 ORFs Genes are expressed in a regulated cascade Some fulfill regulatory functions pUL38 expression during early phase pUL38 blocks apoptosis. http://www.abbottdiagnostics.co.uk. Tuberous Sclerosis Complex. Autosomal dominant disorder - PowerPoint PPT PresentationTRANSCRIPT
HCVM
• Member of -herpesvirus family
• >200 ORFs• Genes are expressed in a
regulated cascade• Some fulfill regulatory
functions• pUL38 expression during
early phase• pUL38 blocks apoptosis
http://www.abbottdiagnostics.co.uk
Tuberous Sclerosis Complex
• Autosomal dominant disorder
• Characterized by benign tumors
Due to inactivating mutations in TSC1 or TSC2
• Conserved signaling pathway that regulates cell growth
• TSC1/TSC2 functions as GAP towards Rheb
Identification of pUL38 interacting proteins
• pUL38 is expressed under proper kinetics and at normal levels
• Isolation by immuno- affinity purification
• Separation by gel electrophoresis
• Identification by sequential MS and MS/MS analysis
~ 50 target proteins
pUL38 interacts with the TSC2 but not with the TSC1 protein
293T, Transfection of a vector expressing pUL38, 48 hrs p.t.
Summary
• pUL38 interact via TSC2 with the TSC1/2 complex
• Ectopic expression of pUL38 in fibroblasts increased their size
• Interaction of pUL38 with TSC1/2 blocked its ability to regulate mTORC1 in response to stress outside the context of infection
• In the presence of pUL38, AMPK stimulation did not block phosphorylation of rpS6